Siddharth Ramakrishnan

Updated: October 2013

The main focus of the laboratory is funded through the NSF Early CAREER award to Dr. Siddharth Ramakrishnan (2013-2018) and will focus on the Modulation of the Reproductive Neuroendocrine System by Endocrine Disruptors

Gonadotropin releasing hormone (GnRH) neurons in the brain are the primary controllers of reproduction and associated behaviors in most vertebrates and invertebrates studied. Problems related to reproductive health, fertility and behavior have links to abnormal development and function of the GnRH neuronal system. There is increasing evidence that endocrine disrupting (ED) chemicals (such as bisphenol A, pthalates. PCBs) in our environment, from industrial effluents, sewage etc., have deleterious effects on the reproductive systems and reproductive behaviors in many species. While there is evidence for the impact of EDs on reproductive behavior, development and adult function, few studies examine the effects of EDs on GnRH neuron embryonic development, GnRH neuron physiology, and correlating with adult behavior.

In the lab transgenic lines of zebrafish and medaka with GnRH neurons tagged with green fluorescent protein will be used to examine effects of chronic exposure to low levels of Bisphenol A (BPA), a synthetic estrogen, on a) GnRH neuron embryonic development, b) physiology of adult GnRH neurons and c) behavior (social/mating) of animals. The studies will span GnRH neuronal development and morphology, physiology through electrical recordings, and behavioral effects on the animal. Confocal imaging of the developing GnRH neuroendocrine system, immunohistochemical studies of receptors and transmitters associated with the GnRH system, whole cell and loose patch electrophysiology of both embryonic and adult neurons, histochemical observations of gonadal and brain tissue, and behavioral observations of adult social/reproductive behaviors will be used through the studies.

The projects will take a comprehensive look at the effect of BPA on GnRH neuronal development and function from the embryo through growth to reproductive adulthood with scope for trans-generational studies.

The development and modulation of the GnRH neuronal system will be examined during chronic exposure to BPA. The proposed research will be centered around 3 specific aims –

(i) effect of BPA on GnRH neuronal development in the early embryo;(ii) effect of chronic BPA exposure on GnRH neuron physiology as adults(iii) how does chronic low-dose BPA exposure affect growth, reproductive maturation and behavior.

Confocal imaging and immunohistochemistry will be used to study developmental changes in neural morphology and receptor expression. Whole cell and loose patch electrophysiology will be used to analyze neural activity both in adults and embryos. Behavioral observations of adults and larvae and histochemical analyses of gonads will be used to understand reproductive fertlity and behavior as adults. This will be one of the first studies that will address impact of endocrine disruptors on GnRH neuron development, physiology and function in conjunction with whole animal behavior.